Date of Award

5-4-2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Casonya Johnson

Second Advisor

Daniel N. Cox

Third Advisor

Margo Brinton

Fourth Advisor

Sarah Pallas

Abstract

Glia cells are key components of the brain that mediate signaling events between pre- and postsynaptic neurons and that play a vital role in regulating behavior. Depressive disorders are characterized as complex, multifunctional mental disorders that lead to unstable and extreme fluctuation in mood and behavior. Previous studies have shown that loss of glial cells results in emotional and behavioral abnormalities. Here, we exploit the Caenorhabditis elegans model, an optimal system in which to study glia-type specific function because the structure and connectivity of the nervous system has been fully described and previous studies have demonstrated that loss of glia is not lethal and does not result in death of the associated neuron. Because of the predetermined cell lineage, C.elegans neurons do not require trophic support from glia. This provides the advantage to separate the supportive role of glia and focus on understanding how glia regulate behavior.

My dissertation research aims to identify the influence of a glia-subtype, the Cephalic sheath glia (CEPglia), and a glia specific basic helix-loop-helix (bHLH) transcription factor, HLH-17, in regulating complex and rhythmic behaviors. Complex behaviors integrate multiple sensory modulatory inputs to orchestrate a specific motor output. Similarly, rhythmic behaviors utilize an intrinsic pacemaker to modulate periodic activation of a stereotyped sequence of behaviors. Work from our lab demonstrates that the unique expression of HLH-17 in an astrocyte-like cephalic sheath (CEPglia) is required to modulate dopamine-dependent behaviors such as swimming, egg laying, and paralysis; and that HLH-17 regulates the expression of genes required for mating and defecation. Results from my research suggest that expression of HLH-17 in the CEPglia may be required for regulating the precision and accuracy of independent motor programs and that CEPglia coordinate multiple motor responses. Findings from my work outline a hypothetical model by which astrocyte-like CEPglia modulate the function of motor neurons, in part, by transmitting signals through interneurons to motor neurons that are required for behavior. Additionally, my dissertation research hints at a mechanism in which glia may exert sexually dimorphic regulation of a rhythmic behavior.

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